Genetics of Reproduction
Differences in ovarian morphology exist at birth, but trying to find genetic markers for traits so heavily influenced by environment proves difficult.
SIOUX FALLS, S.D. (Dec. 3, 2012) — Assisted reproductive technologies, or ARTs, can increase the rate of genetic improvement in beef cattle, but there are some cautions to keep in mind, Robert Cushman said. A reproductive physiologist at the Roman L. Hruska U.S. Meat Animal Research Center (USMARC) in Clay Center, Neb., Cushman explained that reducing the number of influential parents increases the risk of propagating a lethal recesssive gene, and placing embryos in culture during in vitro fertilization (IVF) can actually change the way genes are expressed and the way they function.
While cautions, these are not reasons to fear ARTs; they are reasons to incorporate genomic technologies into ART, Cushman said. “If we continue to understand what the genome is telling us and how we can use the genome, then we can potentially improve our assisted reproductive technologies.”
Cushman explored what is known about the genetics of reproduction during the 2012 Applied Reproductive Strategies in Beef Cattle (ARSBC) symposium in Sioux Falls, S.D., Dec. 3-4.
We know that reproductive traits are lowly heritable, Cushman noted. They are polygenic, meaning many genes have small effects. In addition, there are large environmental effects, including nutrition and animal health, that contribute to whether a cow conceives.
Culling every open heifer in your herd every year will not create a herd with a 100% pregnancy rate, Cushman said.
“A true inherent failure of fertility doesn’t happen very often,” Cushman said, noting that only about 1% of heifers will fail to conceive in two consecutive breeding seasons. Most of the time, failure to breed is a result of environmental factors.
Cushman agreed with other ARSBC speakers who said genetic markers for production traits would likely be adopted first because they provide economic benefits more quickly. However, in adopting those genetic markers, cattlemen need to keep an eye on how they affect fertility.
We don’t know that in stacking genes for production traits we won’t negatively impact fertility, Cushman said. Whether talking panels of genes or ascertaining net merit with indices, he encouraged inclusion of whatever markers are available for fertility — even if the goal is not to improve fertility, but to make sure we don’t negatively impact fertility.
“Genetics are not easy,” Cushman added, pointing to the low heritabilities of pregnancy (7%) and stayability (15%). Heritabilities of traits related to heifer development are higher (see Table 1), offering potential to find genetic markers to foster improvement.
Table 1: Heritability of reproductive traits
|Age at first ovulation||
|Mialon et al., 2001|
|Age at first progesterone||
|Mialon et al., 2001|
|Age at puberty||
|Snelling et al., 2012|
|Morris et al., 2000|
|Reproductive tract score||
|Martin et al., 1992|
|Yearling uterine horn diameter||
|Johnston et al., 2009|
|Antral follicle count||
|Snelling et al., 2012|
|Age at first calving||
|Minick Bormann and Wilson, 2010|
|Heifer pregnancy rate||
|Doyle et al., 2000|
|Thallman et al., 1999|
|MacNeil et al., 2006|
|Doyle et al., 2000|
Sources: Cushman et al., 2008. R Bras Zootec 37:116
Differences in ovarian morphology exist at birth, Cushman said. In studies looking at ovaries removed from newborn heifers, some heifers had ovaries twice as heavy with more antral follicles (the large follicles visible by ultrasound that contain an egg) than others. That begs the question, when does heifer development start?
“Heifer development starts when the undifferentiated gonad actually starts to turn her into a female,” Cushman said, referring to cellular development of the reproductive tract. There are a host of growth factors that affect sexual differentiation from an undifferentiated gonad to a very infantile tract to a more mature male or female tract.
“If you start deleting certain genes at the upper end before the gonad has differentiated, you can have a double effect,” Cushman said, noting results of small testes and fewer sperm in males, and small ovaries and fewer or no follicles in females. “If you are at a high enough region in that genetic path and you turn genes off or alter their effect, you can influence gonadal development no matter which direction they’re going in (male or female), which to me is that connection that we see, at least genetically, between scrotal circumference, age at puberty and female performance.”
According to USMARC data, females that calve early as heifers will be more likely to stay in the herd to 5 years of age, and they will continue to wean a heavier calf through their fifth or sixth calf. That affects your bottom line, Cushman said. But how do you select for heifers that will calve early other than by selecting the biggest — and theoretically oldest — heifers, which can have negative repercussions on cow size.
One option is to breed all the heifers, then pregnancy-check them by ultrasound at 21 days and keep those that conceive. Another option is to limit the breeding season to 21 days, keeping only those that conceive. Reproductive tract scores (RTS) provide another good way to analyze reproductive development.
Using ultrasound to assess the antral follicle count (AFC) can also provide an idea of reproductive capacity, Cushman said. Heifers are born with about 100,000 primordial follicles. Studies have shown that heifers with more than 100,000 primordial follicles also had more secondary follicles and more antral follicles than heifers born with fewer than 100,000.
In his research, Cushman used ultrasound to classify heifers as low-AFC (fewer than 15 antral follicles) or high-AFC (more than 25 antral follicles). The difference in subsequent pregnancy rates was 85% for the low-AFC heifers and 95% for the high-AFC heifers.
While a 10% difference in pregnancy rate is substantial, it doesn’t mean that the low-AFC heifers were infertile, Cushman emphasized. An 85% pregnancy rate means those heifers were fertile. The high-AFC group was just more fertile — and for reasons still to be discovered.
In another study comparing AFC of heifers calving in the first, second or later 21-day period, heifers calving in the first 21 days had a four-follicle advantage in AFC.
While there is a correlation between AFC and histology, AFC only predicts about 30% of the variation in ovarian reserve, Cushman said, pointing to the need for other predictors, preferably combined in a panel of traits that can explain a greater percent of the variation in fertility.
“Variation in the genetic sequence that results in a change in the function of the encoded protein makes the best genetic markers because their identity and function can be clearly understood,” Cushman explained in his proceedings paper. “However, the identification of functional polymorphisms within a gene is the most difficult aspect of this work.”
Progress is being made, especially in human research, in the area of pharmacogenetics — a concept that you can tailor hormonal or medicinal doses to a person based on their genetic makeup, Cushman noted. Common hormones used in synchronization and superovulation — gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and prostaglandin F2α (PG) — all work through protein receptors. Different genotypes for a receptor may function differently, changing the dose of hormone needed.
To explain variation in ovulatory response due to superovulation, USMARC researchers conducted a whole-genome scan and worked their way down to a gene on chromosome 6. The polymorphism in the ionotropic glutamate receptor AMPA1 (GRIA1) had previously been reported by Sugimoto et al. as a functional polymorphism, changing the amino acid sequence. The researchers reported that animals homozygous for the serine amino acid and heterozygotes had antral follicle counts up around 20. Cattle homozygous for asparagine, which changed the receptor, had lower AFC. The researchers proposed the change to asparagine changed the binding affinity of the hormone receptor. They reported decreased GnRH secretion, a decreased luteinizing hormone (LH) surge after synchronization with PG and decreased AI conception.
A USMARC study found no difference in the AFC of beef cows carrying the polymorphism vs. those that didn’t; however, when they compared repeat breeder cows (cows that failed to conceive in two breeding seasons) to cows that had calved throughout their lifetime, the repeat breeders had fewer follicles. There was no difference in age at first breeding, but the repeat breeders were about 40 days older at first calving. Their ovaries were smaller and the diameter of the uterine horns was smaller.
Cushman spoke during Monday's session
Comprehensive coverage of the symposium is available online at www.appliedreprostrategies.com. Compiled by the Angus Journal editorial team, the site is made possible through sponsorship by the Beef Reproductive Task Force and LiveAuctions.tv.
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